Mastocytosis/ Mast Cell Activation Disorders > FAQs > Mastocytosis FAQ
Frequently Asked Questions about Mastocytosis
What does a rising tryptase level mean?
Does an increasing tryptase level mean the disease is getting worse?
Will more medication keep my tryptase level from rising — or at least slow it down?
Are people who have higher tryptase levels sicker?
What is the difference between indolent and smouldering mastocytosis?
Question: I am still new to all of this. I know that tryptase levels rise when you are having an attack, but should your resting tryptase level rise?
Answer: Tryptase is one of the substances that mast cells manufacture and store in granules inside the cell, and when mast cells degranulate (that is, release the contents of their granules outside the cell), tryptase is usually released.
A mast cell can degranulate completely (as when a person has anaphylaxis) or partially (as when they have a milder allergic or inflammatory reaction).
When a person who does not have mastocytosis has anaphylaxis or hives, their levels of tryptase can rise dramatically, but this increase is only temporary, usually lasting no more than several hours.
Meanwhile, even when not having anaphylaxis or any other kind of reaction, a person with mastocytosis will have tryptase levels that are higher than those of someone who does not have mastocytosis.
Why? Well, even when you're not having anaphylaxis, some mast cells will be degranulating, at least partially, for one reason for another. So while a non-masto person's normal tryptase is quite low (15 ng/mL or less), a person with mastocytosis's tryptase level will reflect roughly how many excess mast cells they have in their body. If you have systemic mastocytosis, usually your baseline level of tryptase will greater than 20 ng/mL.
So, specialists use the tryptase level of a person with mastocytosis to estimate the person's overall "mast cell burden" — that is how many mast cells the person has. This mast cell burden measurement has to be made when the mastocytosis patient is not having anaphylaxis or a hypotensive episode.
A few technical notes (ignore them if they're over your head):
- Basophils, which are in some ways similar to mast cells, contain only 1/500th as much tryptase, and so tryptase release reflects mast cell activation much more than basophil activation.
- People who are not diagnosed with mastocytosis but who have tryptase levels between 10 and 20 ng/ML are at increased risk for more severe anaphylactic reactions.
- Tryptase levels can rise in people who do not have mastocytosis. For example, a person with end-stage kidney disease may have elevated tryptase levels. This is one reason why a thorough work up is needed before the diagnosis of mastocytosis is made.
Reference: Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunology & Allergy Clinics of North America 2006; 26:451-63.
Question: My tryptase level is not really high to begin with. It started at 22, but it has gone up to 29. One doctor told me that is how he will track the progression of the disease. If my tryptase level is rising is the disease getting worse?
Answer: The increase does suggest that you have more mast cells, and people with mastocytosis do tend to accumulate more mast cells over time. However, in people who have so-called indolent mastocytosis this process seems to be somewhat self-limiting. In other words, it's not like having cancer or leukemia.
An increase from 20 to 29 suggests your doctor should keep an eye on your tryptase levels, but 29 is still not really high. In a study I read recently, the mean tryptase level for a group of 17 patients with systemic mastocytosis was 100.
Reference: Proelss J, Wenzel J, Ko Y, Bieber T, Bauer R. Tryptase detection in bone-marrow blood: a new diagnostic tool in systemic mastocytosis. Journal of the American Academy of Dermatology 2007; 56:453-7.
Question: If my tryptase level is rising, does more medication slow down this process?
Answer: Symptomatic medications (such as mast cell stabilizers, H1 and H2 antihistamines, leukotriene inhibitors, NSAIDs, glucocorticoids, bisphosphonates, and epinephrine) do not slow the increase in the number of mast cells — rather they either treat the symptoms caused by mast cell degranulation or make the mast cells less likely to degranulate.
What are called cytoreductive treatments can actually reduce the number of mast cells. However, they are not usually used in people with "low-grade" (that is, "indolent") mastocytosis because of the increased risk of making things worse or of developing "secondary leukemias." An exception is sometimes made, however, for what is called smouldering systemic mastocytosis.
Reference: Wilson TM, Metcalfe DD, Robyn J. Treatment of systemic mastocytosis. Immunology & Allergy Clinics of North America 2006; 26:549-73.
Question: Are people who have higher tryptase levels sicker?
Answer: On average, I would say that the greater the mast cell burden, the more problems a person is going to have, but this disease affects different people very differently. It's dangerous to make a generalization because usually three people will pop up to tell you that you don't know what you're talking about! There are people out there, walking around, who have full-blown systemic mastocytosis and don't even know it. In other words, there are people with increased mast cell burdens who don't really have enough symptoms to go see a doctor about them!
Question: What is the difference between indolent mastocytosis and smouldering mastocytosis?
Answer: People with Smoldering Systemic Mastocytosis (SSM) meet the criteria for Systemic Mastocytosis and usually have at least two of the following findings:
- Infiltration grade (MCs) in greater than 30% in bone marrow in histology and serum total tryptase levels greater than 200 ng/mL. (In laymen's terms: More than 30% mast cells infiltrating bone marrow and tryptase over 200 ng/mL.)
- Hypercellular marrow with loss of fat cells, discrete signs of dysmyelopoiesis without substantial cytopenias or WHO criteria for an MDS or MPD. (Tough to translate into simple language!)
- Organomegaly: palpable hepatomegaly, splenomegaly, or lymphadenopathy (on CT or ultrasound) greater than 2 cm without impaired organ function. (In laymen's terms: Noticeably swollen liver, spleen or lymph glands (more than 3/4"), but without problems in organ function.)
Reference: Valent. Diagnostic Evaluation and Classification of Mastocytosis. Immunology & Allergy Clinics of North America 2006; 26:515-34.