Labs
Diagnosing Mast Cell Activation Syndrome (MCAS) is notoriously challenging, as symptoms are often intermittent and can affect nearly every organ system.
There is no single definitive test; instead, diagnosis relies on a combination of clinical history, symptom patterns, and laboratory markers. Lab tests may include serum tryptase, plasma histamine, prostaglandin D2, chromogranin A, and urinary markers such as N-methylhistamine or 11β-PGF2α—ideally collected during or shortly after a flare. However, these markers can fluctuate and may be normal between episodes, making timing and clinical context crucial. A diagnosis is typically made when there is clear evidence of mast cell mediator release, consistent symptoms, and a positive response to medications that stabilize mast cells or block histamine.
Serum Tryptase (blood test)
Tryptase is the most stable and reliable marker of MCAS. It is the mast cell chemical that is the most useful clinically, although we don’t know its full biological function. Both immune cells basophils and mast cells contain tryptase, but mast cells have 500 times more, making it specific to mast cells.
The gold testing standard of tryptase is The 20% + 2 Rule.
Let me explain. Add 20% more than your own baseline level of tryptase then add another 2 points and boom you’ve got MCAS?
Yes.
Although you’re not done testing yet. You need two tests. One tryptase test when you are in a flare of symptoms and one at a low-to-no symptom baseline.
When you’re measuring in a flare, a tryptase level should be measured within four hours (ideally 1-2 hrs) after symptom onset, when possible, to provide evidence that mast cells are responsible for your symptoms. This can be challenging to get to a lab or hospital quickly enough to have your sample taken. That’s one reason we advocate for your healthcare provider to provide a requisition form to you well in advance of a flare. Please consider asking them for one.
If you are fortunate enough to get tested, here are some examples of a positive result during a flare.
Imagine your baseline tryptase is 8 ng/mL:
8 ng/ml x 1.2 + 2 = ≥ 11.6 ng/ml
What if your tryptase was 15?
15 ng/mL x 1.2 + 2 = ≥ 20 ng/mL
What if it’s even higher at 41?
41 ng/mL x 1.2 + 2 = ≥ 52 ng/ mL
The 20% + 2 has been established as a gold standard because it’s able to detect meaningful rises at all levels of baseline tryptase, high, medium or low. No other test can do that, yet.
How reliable is tryptase?
When you compare tryptase levels between people they vary greatly. But when you compare your own levels from one day to the next, there is very little variation in tryptase because it is tightly regulated by our body.
What range is normal?
The normal range of tryptase levels in adults is 1 to 15 ng/mL with the average being 5 ng/mL. Levels greater than 11.5 ng/mL are considered to be elevated, but that’s not to say you have MCAS at this level. You still need the 20% + 2 to be true.
Tryptase is a robust validated test that safely discriminates between MCAS and other non-MCAS allergic conditions. It’s just not tested enough. Let’s change that.
DAO
There’s no conversation about histamine without talking about DAO – Diamino-oxidase, the enzyme that breaks histamine down.
While it does a great job at metabolizing histamine, let me break down why DAO is not a helpful marker for testing MCAS nor Histamine Intolerance.
Validated tests are not generally available, but that doesn’t mean you can’t find DAO tests. Just because they exist, doesn’t mean we can trust them. We have no ability to correlate blood levels of the enzyme to intestinal levels of it, where it’s mostly active.
DAO testing might be helpful to supplement a clinical diagnosis, but really has no place in the diagnosis of MCAS or Histamine Intolerance.
Total IgE
MCAS – Multiple food and environmental intolerances with negative IgE testing usually does NOT warrant further evaluation of MCAS as the primary origin of symptoms.
IgE levels may be lower in MCAS patients because of the adsorption of IgE onto the increased numbers of mast cells, making it less available for detection in serum.
Adsorption is the physical adherence or bonding of ions and molecules onto the surface of another molecule. Meaning, IgE proteins can get all used up and unmeasurable because they are busy sticking to mast cells.
