How to Diagnose Mast Cell Activation Syndrome

How is Mast Cell Activation Syndrome Diagnosed?

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Mitchell Medical Group · Medically reviewed by Dr. Dean Mitchell, MD · Last reviewed July 25, 2026

Diagnosing Mast Cell Activation Syndrome (MCAS) requires meeting three core criteria: (1) recurring symptoms consistent with mast cell mediator release affecting two or more organ systems, (2) laboratory evidence of elevated mast cell mediators during or after a symptomatic episode, and (3) a positive response to mast cell-targeted treatment. In practice, the second criterion is the hardest to satisfy — mast cell mediators break down quickly and are frequently not captured even in patients who clearly have the condition, which is why the medical history carries most of the diagnostic weight. Because MCAS mimics dozens of other conditions, diagnosis is often delayed — but with a physician experienced in mast cell disorders, a clear picture typically emerges within a few appointments.

“The history is probably 90% of the way of making the diagnosis.”  — Dr. Dean Mitchell, M.D.

It’s actually common for patients with mast cell activation syndrome to consult with many doctors before finding one who can correctly diagnose this condition. This happens because there are typically lots of symptoms that look like other conditions, and it’s hard to pinpoint their exact cause. Mast cells are allergy cells responsible for immediate allergic reactions so it commonly masquerades as a severe allergic reaction.

A lot of patients who have allergic reactions, whether it’s to foods, environmental exposures, or even vaccines, may have mast cell activation syndrome. Now there are some sophisticated tests that we can do in the blood to check for mast cell activation but they’re not always that accurate.

Even testing for MCAS can be a challenge because we are testing for the mediators – the chemicals that the mast cells are releasing. And many of them are thermolabile so heat destroys them very quickly or they have a very, very short half-life. To catch them in a urine or blood test can be difficult. So sometimes the first round of testing comes back negative but it doesn’t mean you don’t have MCAS. We simply haven’t been able to prove it.

Negative testing also raises a separate question worth answering before you go further: whether what you have is MCAS, histamine intolerance, or a true food allergy — three conditions that look alike but are treated very differently.

What Simple Test Does Dr. Mitchell Use to Check for MCAS?

The test is dermatographism, sometimes called skin writing. The skin is stroked firmly with a fingernail or a blunt edge, and in a positive result the line raises up red and swollen within minutes — clearly enough that a patient can write their name on their own skin. Dr. Mitchell finds it in roughly 90% of the MCAS patients he evaluates, and most of them had no idea they had it.

“I do like to stroke the skin to test for dermatographia. I find that can be a reflection of what’s going on inside their body.”  — Dr. Dean Mitchell, M.D.

A positive result is not a diagnosis on its own, and a negative one does not rule MCAS out. It is one finding read alongside the medical history, which is why it is checked during the consultation.

Believe it or not, one of the easiest ways to have an idea if you should be further evaluated for mast cell activation actually involves simple stroking of the skin.

There are some additional tests that can be utilized to help diagnose mast cell activation syndrome (MCAS) such as:

• Tryptase levels: a 20% rise even if in normal level
• 24-hour urinary prostaglandin D2
• Histamine in the blood greater than 8nmol/L
• MMP-9 greater than 400

But I have found this skin stroke test to be the most reliable for helping to identify if further evaluation is needed to diagnose this chronic condition. And like all the other conditions I treat, I start with a very comprehensive medical history from each patient to better understand your health throughout your life.

“MCAS is multi-systemic. Someone with MCAS may have a history of frequent infections, a history of bladder issues or urinary tract issues. A patient may have issues with asthma or their joints or migraines. Fatigue is probably one of the most common symptoms I see with MCAS. When I start to hear things that are involving multiple areas of their body right away, I know it’s multi-system. And we know MCAS is a multisystem inflammatory condition. I hear inflammation – I hear multiple systems.” – Dr. Tania Dempsey

What are the Symptoms of Mast Cell Activation Syndrome?

Mast cells are present in virtually every tissue in the body and release mediators which can have a range of effects on other cells which means that there are a multitude of symptoms associated with MCAS.

If you suffer from the following symptoms, you may have MCAS.

• Skin Issues: hives, flushing, itching, rashes
• Gastrointestinal (GI) Issues: bloating, reflux, nausea, diarrhea
• Respiratory Issues: sneezing, wheezing, shortness of breath
• Cardiac Issues: palpitations, chest pain, low blood pressure; chest discomfort
• Swelling or tingling in any part of the body
• Lightheadedness or headaches
• Environmental allergies
• Easy bleeding or bruising
• Poor healing

Symptoms can start at any age but are most often present in adulthood.

If you think you may be suffering from mast cell activation syndrome schedule an appointment with a doctor who specializes in diagnosing and treating mast cell activation in your area or schedule an in-person or virtual consultation with Mitchell Medical Group.

What Makes Dr. Mitchell’s Approach to Diagnosing MCAS Different?

You give your medical history to Dr. Mitchell directly. There is no medical assistant, resident, or care-team member who takes the history and relays it to him — he listens to the entire history himself, in every consultation.

For a condition where the history is 90% of the diagnosis, that is not a matter of courtesy. It is the diagnostic method.

“That’s why I listen to the history from the patients directly myself the entire time. I think it’s one of the most important parts of making the diagnosis.”  — Dr. Dean Mitchell, M.D.

The detail that identifies the pattern is rarely the one a patient expects — a reaction three hours after dinner rather than three minutes, an antibiotic that caused hives years earlier, a stretch of unexplained fatigue that began after a move.

“I have to hear all the small details that will give me clues.”  — Dr. Dean Mitchell, M.D.

For more resources on Mast Cell Activation Syndrome check out mastcellaction.org.

Frequently Asked Questions

What are the diagnostic criteria for MCAS?

MCAS is formally diagnosed when three criteria are met: (1) recurrent symptoms consistent with mast cell mediator release affecting two or more organ systems, (2) laboratory evidence of elevated mast cell mediators collected during or shortly after a symptomatic episode, and (3) a positive response to mast cell-stabilizing or mast cell-targeted treatment. Meeting all three is what distinguishes MCAS from other mast cell-related conditions. In practice, the second criterion is the hardest to satisfy, because mast cell mediators break down quickly and are often not captured even in confirmed cases.

What lab tests are used to diagnose MCAS?

The most common tests include serum tryptase, 24-hour urine prostaglandin D2, N-methylhistamine, and heparin levels. Because mast cell mediators break down quickly, timing matters — samples collected during or immediately after a flare yield more accurate results than baseline testing alone. Dr. Mitchell orders tryptase for nearly every suspected MCAS patient, primarily to rule out two other conditions: mastocytosis, meaning too many mast cells, and alpha hereditary tryptasemia, known as alpha-HAT. These tests support the diagnosis but rarely establish it on their own.

How long does it take to get an MCAS diagnosis?

In Dr. Mitchell’s practice the clinical picture usually comes together during the first full consultation, because the medical history accounts for roughly 90% of the diagnosis. Confirmation then comes from the response to treatment, and patients generally respond within one to two weeks. Many MCAS patients have seen multiple providers before receiving a correct diagnosis, largely because the symptoms overlap with so many other conditions — but that delay reflects how rarely the condition is considered, not how long the evaluation itself takes.

Can MCAS be diagnosed without a specialist?

A primary care physician can initiate the diagnostic workup, but MCAS is most accurately confirmed by a physician experienced in mast cell disorders. A specialist can interpret mediator lab results in context, recognize atypical presentations, and design a targeted treatment protocol — which is itself part of the diagnostic confirmation process. Dr. Dean Mitchell evaluates MCAS patients at his Manhattan office on West 57th Street, at his Rockville Centre office on Long Island, and by telehealth for patients elsewhere in the country.

Can you have MCAS with a normal tryptase level?

Yes. A normal tryptase level is common in Mast Cell Activation Syndrome and does not rule the condition out. Tryptase is one of many mediators stored inside mast cell granules, and most MCAS patients test in the normal range. A markedly elevated tryptase raises concern for a different mast cell disorder such as mastocytosis. A normal result means the blood test did not capture what the patient is experiencing, which is why the medical history carries most of the diagnostic weight.

What is the skin writing test for MCAS?

Dermatographism, sometimes called skin writing, is a bedside test in which the skin is stroked firmly with a fingernail or a blunt edge. In a positive test the stroked line raises up red and swollen within minutes, clearly enough that a person can write their name on their own skin. Dr. Mitchell finds this present in roughly 90% of the MCAS patients he evaluates, and many of them had no idea they had it. It is one finding read alongside the history, not a diagnosis on its own.

What does MCAS get misdiagnosed as?

More often than receiving a wrong diagnosis, MCAS patients receive no diagnosis at all. Dr. Mitchell describes patients being dismissed and referred to psychiatry, because the symptoms they report most often — brain fog and fatigue — cannot be measured or observed the way a physical finding can. Reactions occurring hours after eating rather than minutes are also frequently ruled out as food allergy when standard allergy testing returns normal, which it usually does in MCAS.

Can MCAS be diagnosed through a telehealth appointment?

Yes. Because the medical history carries roughly 90% of the diagnosis, MCAS evaluation translates well to telehealth, and Dr. Mitchell sees mast cell patients from across the country by video. Patients in the New York area can be seen in person at the Manhattan office on West 57th Street or at the Rockville Centre office on Long Island. Where a physical finding such as dermatographism is relevant, it can often be demonstrated by the patient on camera.

 

Mast Cell Activation Syndrome Podcast Episodes

Want to know more about MCAS. Check out the following podcast episodes on Mast Cell Activation on Spotify.

• Making the Difficult Diagnosis of Mast Cell Activation Syndrome with Dr. Tania Dempsey
• Mast Cells: How They Affect Vaccine, Drug & Food Allergies with Dr. Mariana Castells
• Complex Medical Cases: Toxic Mold, Candida, CFIDS & Mast Cell – How are They Related with Dr. Neil Nathan
• Low Histamine Diet & Mast Cell Activation Syndrome with Dr. Lawrence Afrin

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About Dr. Dean Mitchell, MD  —  Board-Certified Allergist & Immunologist

Manhattan & Rockville Centre, Long Island · Telehealth nationwide · 30+ years in practice · Sackler School of Medicine · Robert Cooke Allergy Institute · Adjunct Clinical Professor, Touro College of Osteopathic Medicine · Fellow, AAAAI

He has spent years diagnosing and treating Mast Cell Activation Syndrome (MCAS) — including patients who went undiagnosed for years because MCAS overlaps with so many other conditions — and sees new MCAS cases in his practice every week.

You work directly with Dr. Mitchell. He takes every patient’s full medical history himself, in every consultation — there is no medical assistant or trainee taking your history and relaying it back, and no patient care team in between.

Specialties:  Candida & microbiome  ·  MCAS  ·  Toxic mold illness / CIRS  ·  Food allergies  ·  Allergy drops (SLIT)

Featured in:  New York Times · Daily Mail · SELF · Martha Stewart · HuffPost · Fox News · ABC · Intelligent Medicine Podcast · Natural Awakenings

Podcast:  Host — The Smartest Doctor in the Room  ·  230+ episodes featuring Harvard, Stanford & NIH researchers  ·  Spotify & Apple Podcasts

Books:  Conquering Candida: The New 30-Day Protocol (2025)  ·  The Allergy and Asthma Solution (2006)

References

Mast Cell Action. An organization dedicated to supporting the mast cell disease community.

Healthline: Mast Cell Activation Syndrome: Symptoms and Treatment.

NIH. Genetic and Rare Diseases Information Center. Mast Cell Activation Syndrome.

WebMD: What is Mast Cell Activation Syndrome.

Mast Cell Activation Syndrome (MCAS). American Academy of Allergy Asthma & Immunology.

Mast Cell Activation Syndromes. Cem Akin, PhD. June 2017.