Disclaimer: This article is reviewed by Dr. Titus and is intended for general informational purposes only. It does not constitute medical advice. If you have difficulty breathing, a feeling of your throat closing or sudden dizziness, go to the nearest emergency department.
Key Takeaways
Mast Cell Activation Syndrome
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MCAS is a real but rarely confirmed condition where mast cells release histamine for no clear reason. That’s what separates it from an allergy, which has a trigger.
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Symptoms like flushing, itching, rashes, fatigue and diarrhoea are common to many conditions, so having them doesn’t mean you have MCAS.
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It can only be diagnosed by an immunologist, after other causes are ruled out, including serious ones like certain cancers. A GP is the first step for a referral.
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MCAS is likely over-diagnosed online. There’s no scientific evidence linking it to EDS or POTS, and the long COVID link is still debated.
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Treatment is usually antihistamines. There’s no robust evidence that a low-histamine diet helps. There’s no cure, but long-term remission is possible.
What is mast cell activation syndrome (MCAS)?
Quick Answer: MCAS is a condition where mast cells, immune cells that release histamine, are activated inappropriately.
Mast cells are white blood cells that release histamine. They are often involved in allergic reactions, although, as Dr. Titus points out, that is not their primary purpose in the immune system.
Many conditions cause mast cells to activate inappropriately, allergies being the most common. That is why MCAS is what doctors call a diagnosis of exclusion.
According to the Australasian Society of Clinical Immunology and Allergy (ASCIA), other mast cell disorders must be ruled out first. Only then is a patient assessed against a strict set of criteria, proposed by an international consensus group in 2012 and since validated in multiple studies.
What are the symptoms of MCAS?
Quick Answer: Symptoms come from histamine release, and can affect the skin, gut, energy levels and more.
Reported symptoms include:
- Flushing and itching
- A variety of rashes
- Chronic fatigue and headaches
- Light-headedness, from low blood pressure
- Diarrhoea
- Fibromyalgia-like pain
- Neuro-psychiatric symptoms
- Intolerances to foods, medications or environmental factors
The catch, Dr. Titus notes, is that “many of these symptoms are not specific and can be attributed to many other diseases.” Having several of them does not mean you have MCAS.
Is MCAS the same as an allergy?
Quick Answer: No. An allergy has a trigger. MCAS is mast cells activating without a good reason.
Both involve mast cells releasing histamine, but they are not the same thing. “An over-simplified way to think about it is that MCAS is a condition when mast cells are activated without any good reason,” Dr. Titus explains. With an allergy, there is a clear trigger, such as a food or pollen.
It also works the other way: MCAS cannot be diagnosed if a known mast cell disorder is already present.
If you’re trying to work out what’s behind a reaction to food, our article on whether organic food helps with allergies or sensitivities explains the difference between reacting to a food and reacting to something on it.
What triggers MCAS flare-ups?
Quick Answer: There is surprisingly little research on this. Dr. Titus’s view is that flares most likely come from histamine not being suppressed enough.
Because MCAS is defined as mast cells activating without a good reason, there is no clear list of triggers to avoid in the way there is with an allergy. Dr. Titus says there is not much published on what causes flare-ups.
In his view, the most likely explanation is insufficient histamine suppression, either because medication is not being taken consistently, or because a stronger treatment is needed.
In practice, that means taking your antihistamines as prescribed, and going back to your immunologist if flares keep happening despite that.
How is MCAS diagnosed, and why is it so hard to confirm?
Quick Answer: Other conditions with similar symptoms have to be ruled out first, including some serious ones. Only then can MCAS be confirmed.
Ruling out other mast cell disorders is only the first step. Many other conditions mimic the symptoms of MCAS, ranging from the benign, like menopause, to serious ones such as neuroendocrine tumours, thyroid cancer and lymphoma.
That is the main reason MCAS is hard to confirm, and why doctors are cautious about it. As Dr. Titus puts it: “It would be a great tragedy to diagnose someone as having MCAS whilst missing the serious and potentially fatal cancer.”
Ruling out other conditions usually involves blood tests. Our guide to understanding abnormal blood test results can help you make sense of what your doctor is looking at.
Is MCAS real, or is it over-diagnosed?
Quick Answer: “MCAS is real. There is a good chance that it is over-diagnosed.”
ASCIA’s position paper notes that many patients with symptoms that look like MCAS do not meet the diagnostic criteria once other causes have been properly investigated.
What about EDS and POTS?
MCAS is often mentioned online alongside Ehlers-Danlos syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS). According to Dr. Titus, there is currently no scientific evidence that either condition is linked to dysregulated mast cells. ASCIA is clear that they should not be used as part of the criteria for diagnosing MCAS.
What about long COVID?
Some studies suggest long COVID may cause MCAS through immune dysregulation, but this is controversial.
The British Society for Allergy and Clinical Immunology (BSACI) notes that while COVID and many other infections can cause hives and swelling similar to MCAS, this is usually limited to the acute phase of the illness.
Dr. Titus adds that even if long COVID did lead to a mast cell disorder, it would count as a secondary cause of mast cell activation rather than MCAS itself, though he admits “this is probably just semantics at this point.”
For another doctor’s take on separating evidence from online claims, see our guide to Crohn’s disease treatments, which looks at stem cells, FMT and hyperbaric oxygen.
Who should I see for MCAS? Can a GP help?
Quick Answer: Only an immunologist should diagnose MCAS. A GP can refer you, and help monitor your symptoms afterwards.
If you suspect MCAS, start with your GP. “A GP can help by referring patients to an immunologist for further assessment,” Dr. Titus says, “and can also help with ongoing monitoring of symptoms after the diagnosis has been made.”
If you’re being referred to an immunologist, our comparison of public vs private specialist care in Singapore can help you decide which route suits you.
How is MCAS treated?
Quick Answer: Usually with antihistamines. If those are not enough, an immunologist may try medications that target mast cells more directly.
Antihistamines are the first-line treatment. If they do not control symptoms well, immunologists may add other medications that specifically target mast cells and histamine release.
Does a low-histamine diet help MCAS?
Quick Answer: There is no robust evidence that it does, and it is not recommended as a way to manage MCAS.
Low-histamine diets are widely promoted online, but Dr. Titus says there is currently no robust evidence that changing your diet manages MCAS effectively. ASCIA’s position paper reflects this, and does not recommend dietary changes as a treatment strategy.
When should I see a doctor about flushing, hives or reactions?
Quick Answer: If your symptoms are bothering you, see a doctor.
“Different people have different thresholds,” Dr. Titus says. “If your symptoms are bothering you, you should definitely seek medical attention.” You do not need to wait until symptoms are severe, and your GP is the right first stop.
If you’re enrolled in Healthier SG, your regular GP visits may be subsidised, which makes ongoing monitoring easier.
When is an MCAS reaction an emergency?
Quick Answer: Difficulty breathing, a feeling of your throat closing, or dizziness may be anaphylaxis. Go to the emergency department straight away.
Seek emergency care if flushing or hives come with any of the following, as you may be having anaphylaxis:
- Difficulty breathing
- A sensation of your throat closing up
- Dizziness or light-headedness
Can MCAS go away?
Quick Answer: There is no known cure, but many patients manage their symptoms well enough to reach long-term remission.
“MCAS is not known to be curable at present,” Dr. Titus says. “Like many chronic diseases however, patients are able to manage their symptoms well enough to be in long-term remission.”
The Bottom Line
MCAS is real, but it is rarer than the internet suggests, and it can only be confirmed after other causes, some of them serious, have been ruled out. If you recognise the symptoms, the best next step is your GP, who can refer you to an immunologist rather than leaving you to self-diagnose.
Medically Reviewed
About the Expert
Reviewer
Dr Titus Leong
BClinSc/MD — Physician, Flinders University Graduate
Dr Titus Leong is a doctor currently working in Australia with multiple years of clinical experience across both rural and metropolitan settings. A graduate of Flinders University, he works at a tertiary hospital servicing roughly 50,000 inpatients annually and is part of their Basic Physician Training programme.
Written By
About the Writer
Writer
Timothy Leong
Writer, Content Editor & Marketing Specialist — MMC
Timothy Leong is the writer, content editor, and marketing specialist at MMC. With experience in writing and creating websites for local businesses, he makes sure that everything online runs smoothly.
MastCell ActivationSyndrome Doctor Interview
- What is mast cell activation syndrome (MCAS)?
MCAS is as its name suggests; a condition caused by the (inappropriate) activation of mast cells. Put simply, mast cells are white blood cells in our immune system that release histamine and are often implicated in allergic reactions, although that is not it’s primary purpose in the immune system.
Although there are many conditions that result in inappropriate activation of mast cells (a common example being allergies), the diagnosis of MCAS is a diagnosis of exclusion. According to ASCIA (Australian Society of Clinical Immunology and Allergy), other primary, secondary, and well-defined idiopathic mast cell disorders must be ruled out before a diagnosis of MCAS can be made.
Once other mast cell activating disorders have been ruled out, the patient then needs to meet a strict set of criteria to confirm the diagnosis. The diagnostic criteria was proposed by an international consensus group back in 2012 and has been validated in multiple studies.
- What are the symptoms of MCAS?
The symptoms of MCAS relate to the release of histamine by mast cells. These include flushing, itching, chronic fatigue, headaches, a variety of rashes, light-headedness (from low blood pressure), diarrhoea, fibromyalgia-like pains, neuro-psychiatric features, and intolerances to foods, medications, environmental factors. As you might have picked out, many of these symptoms are not specific and can be attributed to many other diseases.
- Is MCAS the same as an allergy?
Although allergies are caused by mast cells inappropriately releasing histamine, they are not the same as MCAS. MCAS cannot exist in the presence of a known mast cell activating disorder. An over-simplified way to think about it is that MCAS is a condition when mast cells are activated without any good reason. Contrast this to an allergy, where there is a trigger (e.g. food, pollen in the environment, etc.) causing the mast cells to be activated and release histamine.
- How is MCAS diagnosed, and why is it so hard to confirm?
To diagnose MCAS, you first need to rule out other causes for its symptoms. We have already mentioned the exclusion of other mast cell activating disorders, but these are not the only conditions that can mimic the symptoms of MCAS. There are a wide variety of conditions with similar symptoms as MCAS. These range from the benign like menopause, to other more serious conditions like malignancies including (but not limited to) neuroendocrine tumours, thyroid cancers, and even lymphomas.
This is probably the reason why it is difficult to confirm a diagnosis of MCAS. Although there is a set criteria to meet to diagnose MCAS, you need to rule out many other more common conditions that can mimic the symptoms of MCAS. And for good reason. It would be a great tragedy to diagnose someone as having MCAS whilst missing the serious and potentially fatal cancer (or endocrine or auto-inflammatory condition).
- Is MCAS real, or is it over-diagnosed? (including the links to long COVID, POTS and EDS)
MCAS is real. There is a good chance that it is over-diagnosed. The ASCIA Position Paper on MCAS mentions that many patients with symptoms reminiscent of MCAS actually end up not meeting the diagnostic criteria for MCAS after extensive investigations to rule out other causes.
There is also currently no scientific evidence that Ehlers-Danlos Syndrome (EDS) or Postural Orthostatic Tachycardia Syndrome (POTS) is associated with dysregulated mast cells or chronic mast cell mediator release. ASCIA is very clear about this and recommends that they are not used as part of the criteria to diagnose MCAS.
Some studies suggest that long COVID infections cause MCAS via dysregulation of the immune system as a part of the disease. This is controversial, with the British Society for Allergy and Clinical Immunology (BSACI) stating that although SARS-CoV-2 and many other infections can cause urticaria and angioedema similar to MCAS, this is usually limited to the acute phase of the reaction itself. It can probably be argued that even if a long COVID infection leads to a mast cell activation disorder, it would then be considered a secondary cause of mast cell activation rather than MCAS. (This is probably just semantics at this point).
- Who should I see for MCAS? Can a GP help, or do I need an immunologist?
MCAS should only be diagnosed by an immunologist. A GP can help by referring patients to an immunologist for further assessment and can also help with ongoing monitoring of symptoms after the diagnosis has been made.
- How is MCAS treated?
MCAS is usually managed with anti-histamine medication, although if this fails to effectively control the symptoms immunologists may try other medication or agents that specifically target mast cells and histamine release pathways.
At present, there is no robust evidence that dietary modification effectively manages MCAS. This is reflected in the ASCIA position paper as well, and as such dietary modification is not recommended as a strategy to manage MCAS.
- When should I see a doctor about flushing, hives or reactions?
Different people have different thresholds. If your symptoms are bothering you, you should definitely seek medical attention. If you have other symptoms such as difficulty breathing, a sensation of your throat closing up, dizziness or light-headedness, you might be having anaphylaxis and should present to the emergency department for further medical attention.
- Can MCAS go away?
MCAS is not known to be curable at present. Like many chronic diseases however, patients are able to manage their symptoms well enough to be in long-term remission.
References
- https://www.allergy.org.au/images/stories/pospapers/ASCIA_HP_Mast_Cell_Disorders_2025.pdf
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3224511/
- https://www.bsaci.org/bsaci-response-to-the-article-nurek-m-rayner-c-fryer-a-et-al-recommendations-for-the-recognition-diagnosis-and-management-of-long-covid-br-j-gen-pract-2021-71e815-e825-published-online-by-bjg/
