How to Improve the Chances of Getting Useful MCAS Test Results
A practical guide to timing, specimen handling, and common pitfalls that can make mast cell mediator testing more or less informative.
Welcome back to The Bendy Bulletin! If you’ve ever been told your mast cell testing was “normal,” you may have assumed MCAS had been ruled out.
Not so fast.
One of the biggest challenges with Mast Cell Activation Syndrome (MCAS) is that obtaining meaningful laboratory results isn’t as simple as ordering the right tests. When the sample is collected, how it’s handled, and even which laboratory performs the testing can all influence the results.
Understanding these limitations can help you have more productive conversations with your healthcare team and improve the chances of obtaining useful laboratory data.
First, an Important Reminder
MCAS is diagnosed based on a combination of your symptoms, medical history, physical examination, and how you respond to treatment. While laboratory tests can help support the diagnosis, no single blood or urine test can confirm or rule out MCAS on its own.
Some patients experience typical MCAS symptoms yet have normal lab results, while others show elevated mast cell mediators that help strengthen the diagnosis. Your doctor will consider lab findings as one important piece of the overall picture, alongside your clinical presentation and treatment response, rather than relying on any single test to make the diagnosis.
Why You Can Have Normal Results Despite MCAS
One of the most common misconceptions is that “normal testing” means you don’t have MCAS.
A negative result doesn’t always mean mast cells aren’t involved. Sometimes it means the testing wasn’t performed under ideal circumstances.
Testing may be less informative if:
Samples are collected when you’re feeling relatively well rather than during a flare
The laboratory doesn’t routinely perform mast cell mediator testing
Specimens aren’t processed or transported correctly
The wrong mediators are ordered
Collection instructions aren’t followed precisely
Many mast cell mediators are fragile molecules that begin breaking down almost immediately after collection. If they aren’t handled properly, the results may not accurately reflect what was happening in your body.
Timing Matters More Than Most People Realize
Unlike many laboratory tests that remain relatively stable over time, mast cell mediators are released intermittently.
Whenever possible, testing should be obtained during or shortly after a significant flare.
That might include episodes of:
Flushing
Itching or hives
Swelling
Rapid heart rate
Feeling faint
Diarrhea or abdominal cramping
Wheezing or shortness of breath
Anaphylaxis-like symptoms
Your healthcare provider can help determine the most appropriate timing based on your individual symptoms.
Which Tests Are Commonly Ordered?
Depending on your clinical presentation, your clinician may consider ordering:
Blood Testing
Baseline serum tryptase
Plasma histamine (less commonly used)
Plasma prostaglandin D₂ (availability varies)
Urine Testing (typically collected over 24 hours)
N-methylhistamine
Leukotriene E₄
2,3-dinor-11β-prostaglandin F₂α
Not every laboratory offers these tests, and availability varies significantly.
Before You Leave the Office
A few simple steps can improve the chances of obtaining useful laboratory results:
☐ My clinician and I discussed whether testing should be performed during a flare.
☐ I confirmed which laboratory will process the specimen.
☐ I verified any special collection or handling instructions.
☐ I know whether I should continue or temporarily hold any medications.
☐ I understand how and when to complete any 24-hour urine collections.
Tryptase: Sometimes Helpful, But Often Misunderstood
Tryptase is probably the best-known mast cell marker, but it’s also one of the most misunderstood.
An elevated tryptase obtained during a flare can provide strong evidence of mast cell activation.
However, many patients with clinically significant MCAS have completely normal baseline tryptase levels.
Key takeaway:
A normal tryptase does not rule out MCAS.
When possible, comparing a baseline tryptase with one obtained during a significant reaction may provide additional information.
One Question Every Patient Should Ask
Before having testing performed, one simple question can help avoid unnecessary problems:
“Does this laboratory routinely perform mast cell mediator testing, and are they familiar with the required specimen handling?”
Depending on the test, proper handling may require:
Collection on ice
Immediate refrigeration
Rapid transport
Frozen processing
Specialized laboratory protocols
These details may seem small, but they can make a meaningful difference in the quality of the results.
Should You Stop Antihistamines Before Testing?
There isn’t one answer that fits everyone.
Some clinicians recommend continuing medications because stopping them could trigger significant symptoms. Others may recommend temporarily holding certain medications when it’s medically appropriate and safe to do so.
Potential medications that may be discussed include:
H1 antihistamines
H2 antihistamines
Cromolyn sodium
Ketotifen
Leukotriene inhibitors
Aspirin
High-dose vitamin C and certain supplements that may influence mediator pathways
Never stop prescription medications without discussing it with your prescribing clinician first.
Build a “Flare Plan” Before You Need One
Because significant flares are unpredictable, many patients find it helpful to prepare in advance.
That might include:
Having laboratory orders already available
Identifying which laboratory will perform the testing
Confirming that the laboratory understands the handling requirements
Reviewing collection instructions before symptoms occur
Planning ahead can make it much easier to obtain testing when the timing is most likely to be informative.
What If Your Results Are Negative?
Perhaps the most important takeaway is this:
Negative mast cell mediator testing does not mean:
Your symptoms aren’t real
Mast cells aren’t contributing
Treatment won’t help
Further evaluation isn’t warranted
Current laboratory testing captures only a small fraction of the hundreds of mediators that mast cells can release. While laboratory data can be helpful, it cannot replace a thoughtful clinical evaluation.
How to Start the Conversation
Rather than asking specifically for an MCAS diagnosis, consider saying:
“I understand that MCAS is primarily diagnosed based on symptoms and clinical evaluation, and that lab testing has its limitations. Given my symptoms, would it be worth discussing whether mast cell mediator testing could be a helpful next step?”
This approach often leads to a more collaborative discussion and acknowledges the complexities involved.
Bottom Line
The goal of MCAS testing isn’t simply to prove or disprove a diagnosis. It’s to collect information that helps your healthcare team better understand what’s happening in your body.
Sometimes laboratory results provide important clues. Sometimes they don’t.
But neither a positive nor a negative result should ever be interpreted in isolation.
Your symptoms, medical history, physical examination, and overall clinical picture remain central to making the diagnosis.
And if there’s one message I’d like you to remember, it’s this:
A normal tryptase does not rule out MCAS.
If you’ve undergone MCAS testing, what do you wish you had known beforehand? And if you haven’t, what questions do you still have? Let’s continue the conversation in the comments.
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We were so fortunate to welcome Dr. Dacre Knight back to Bendy Bodies for an episode packed with practical, evidence-based guidance for the hypermobility community. Dr. Knight tackles some of the most common questions we hear, including whether surgery is truly as risky for people with hEDS as many have been led to believe, when IV vitamin infusions may or may not be appropriate, and what current research is (and isn’t) telling us about the underlying causes of hypermobile Ehlers-Danlos syndrome.
THIS THURSDAY, August 6th: Abbey Phillipson on Awareness, Advocacy, and Every Type of EDS
This Thursday, we’re joined by Abbey Phillipson, founder of the Collagen Advocacy Network, for an important conversation about what growing awareness of hypermobile Ehlers-Danlos syndrome (hEDS) has meant for the broader EDS community. Together, we discuss why diagnostic accuracy matters, how assumptions can impact patient care, and why suffering should never be treated as a competition.
The information provided here is for educational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. No physician-patient relationship is established by reviewing this material. Always consult your own healthcare provider or medical team before making any decisions about medications, supplements, or treatments. Dr. Bluestein is a licensed medical professional, but she is not your personal physician in this context and cannot provide individualized medical care, prescribe medications, order tests, or make referrals outside of a formal clinical relationship.
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Well that’s all for this week; thank you so much for reading and supporting this newsletter. Talk to you soon, Bendy Buddies!
Yours in Health,
Dr. Bluestein
My tryptase level came back normal but the 24 hour urine leukotriene test showed high levels of mast cells. My doctor then ordered a biopsy on an EGD done a few months earlier and also found elevated mast cells. Bingo - 2 areas of significant mast cells - MCAS diagnosis.
Superb advice