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.
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
![Educational infographic explaining that testing for mast cell activation syndrome (MCAS) is most accurate when obtained during or shortly after a significant flare, while symptoms are active. The top section features an illustration of a woman holding her head with a pained expression beside the text, "Testing should be obtained during or shortly after a significant flare. The most accurate results are more likely when testing is done while symptoms are active." A calendar and clock reinforce the importance of timing. Below, eight illustrated panels show symptoms that may indicate a flare: flushing, itching or hives, swelling, rapid heart rate, feeling faint, diarrhea or abdominal cramping, wheezing or shortness of breath, and anaphylaxis-like symptoms. A highlighted red box beside the anaphylaxis panel states, "Seek immediate medical care. These symptoms can be rapid in onset and potentially life-threatening." A banner at the bottom reminds viewers: "If you are experiencing a flare, contact your healthcare provider about testing as soon as possible. Timing matters for the most accurate results." The Hypermobility MD and Bendy Bodies logos appear along the bottom.](https://substackcdn.com/image/fetch/$s_!VawO!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fc4471f50-e393-44c9-a286-b2928cf2ae8b_1122x1402.png "Educational infographic explaining that testing for mast cell activation syndrome (MCAS) is most accurate when obtained during or shortly after a significant flare, while symptoms are active. The top section features an illustration of a woman holding her head with a pained expression beside the text, "Testing should be obtained during or shortly after a significant flare. The most accurate results are more likely when testing is done while symptoms are active." A calendar and clock reinforce the importance of timing. Below, eight illustrated panels show symptoms that may indicate a flare: flushing, itching or hives, swelling, rapid heart rate, feeling faint, diarrhea or abdominal cramping, wheezing or shortness of breath, and anaphylaxis-like symptoms. A highlighted red box beside the anaphylaxis panel states, "Seek immediate medical care. These symptoms can be rapid in onset and potentially life-threatening." A banner at the bottom reminds viewers: "If you are experiencing a flare, contact your healthcare provider about testing as soon as possible. Timing matters for the most accurate results." The Hypermobility MD and Bendy Bodies logos appear along the bottom.")
Your healthcare provider can help determine the most appropriate timing based on your individual symptoms.
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.
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.
![Infographic titled "Before You Leave the Office" with a blue header and checklist icon. The graphic provides a checklist of steps patients can take before laboratory testing to improve the chances of obtaining useful results. The checklist includes: discussing whether testing should be performed during a flare, confirming which laboratory will process the specimen, verifying any special collection or handling instructions, knowing whether any medications should be continued or temporarily held, and understanding how and when to complete any 24-hour urine collections. Each item is accompanied by a simple medical-themed icon and an empty checkbox. The Hypermobility MD and Bendy Bodies logos appear at the bottom of the graphic.](https://substackcdn.com/image/fetch/$s_!k0U4!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F24b036e7-3d8b-4ea4-a716-2a9b6edd0eb7_1024x1536.png "Infographic titled "Before You Leave the Office" with a blue header and checklist icon. The graphic provides a checklist of steps patients can take before laboratory testing to improve the chances of obtaining useful results. The checklist includes: discussing whether testing should be performed during a flare, confirming which laboratory will process the specimen, verifying any special collection or handling instructions, knowing whether any medications should be continued or temporarily held, and understanding how and when to complete any 24-hour urine collections. Each item is accompanied by a simple medical-themed icon and an empty checkbox. The Hypermobility MD and Bendy Bodies logos appear at the bottom of the graphic.")
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.
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.
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.
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.
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.
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.
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.
A huge shoutout to The Bendy Bodies Boutique for supporting today’s newsletter. It’s the perfect place to find something special for the zebra in your life. Explore our newest designs and remember you can personalize any item with your favorite store artwork. From clothing to home goods, there’s something for everyone.
![A mockup of a purple hardcover notebook featuring a cartoon spoon character wearing sunglasses and holding a fork in one hand and a knife in the other, with a determined expression. Large white text on the cover reads, "NO SPOONS LEFT," with the Bendy Bodies logo beneath it. The design is a playful reference to spoon theory, a concept often used in the chronic illness community to describe limited energy reserves.](https://substackcdn.com/image/fetch/$s_!FRYy!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fec4eaf50-c57b-430d-82a2-0e914a255e74_758x986.png "A mockup of a purple hardcover notebook featuring a cartoon spoon character wearing sunglasses and holding a fork in one hand and a knife in the other, with a determined expression. Large white text on the cover reads, "NO SPOONS LEFT," with the Bendy Bodies logo beneath it. The design is a playful reference to spoon theory, a concept often used in the chronic illness community to describe limited energy reserves.")
We were so fortunate to welcome Dr. Dacre Knight back to Bendy Bodies for an episode packed with practical, evidence-based guidance for the hypermobility community. Dr. Knight tackles some of the most common questions we hear, including whether surgery is truly as risky for people with hEDS as many have been led to believe, when IV vitamin infusions may or may not be appropriate, and what current research is (and isn’t) telling us about the underlying causes of hypermobile Ehlers-Danlos syndrome.
![Podcast thumbnail featuring two people wearing headphones on either side of a medical illustration of the back of a person's head and neck, with the cervical spine highlighted in bright red to emphasize pain or injury. On the left is Dr. Linda Bluestein smiling, and on the right is Dr. Dacre Knight. Large text across the center reads, "TOO SOON?" suggesting a discussion about whether it may be too soon to pursue treatment or surgery related to cervical spine conditions. The overall design uses blue tones with the highlighted spine drawing attention to the neck.](https://substackcdn.com/image/fetch/$s_!ocoM!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F79897a35-9f53-4bc4-8266-2057dc77c86d_1280x720.png "Podcast thumbnail featuring two people wearing headphones on either side of a medical illustration of the back of a person's head and neck, with the cervical spine highlighted in bright red to emphasize pain or injury. On the left is Dr. Linda Bluestein smiling, and on the right is Dr. Dacre Knight. Large text across the center reads, "TOO SOON?" suggesting a discussion about whether it may be too soon to pursue treatment or surgery related to cervical spine conditions. The overall design uses blue tones with the highlighted spine drawing attention to the neck.")
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.
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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.
Some of the links shared are affiliate links. If you choose to purchase after clicking a link, I may receive a commission at no extra cost to you that helps support the mission of Bendy Bodies.
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
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