MCAS or CIRS? Mast Cell Activation and Mould Exposure

Mast cell activation syndrome (MCAS) and CIRS (Chronic Inflammatory Response Syndrome) are different diagnoses. But they can look alike, and they may overlap.

• MCAS is diagnosed when repeated attacks of symptoms, such as flushing, hives, stomach cramps, diarrhoea or low blood pressure, come with a measurable rise in mast cell markers in the blood or urine. The symptoms must also get better with treatment aimed at mast cells.
• CIRS is linked to biotoxin exposure, most often in water-damaged buildings. Biotoxins are natural poisons made by living things such as moulds. CIRS is assessed with a vision test and a different set of blood markers.

Mould toxins have been proposed to activate mast cells. So if your histamine-type symptoms began or got worse in a damp building, it is worth looking at both.

If you have read our article on histamine and chronic symptoms, this article continues from there. It explains what MCAS is, how it is diagnosed, what is known about mould and mast cells, and what to ask your doctor.

What is MCAS?

Mast cells are immune cells in the skin, the airways, the gut and around blood vessels. They are the body’s main store of histamine. When they are activated, they also release other chemical messengers: tryptase, prostaglandins, leukotrienes and cytokines [1].

Mast cell activation is a normal part of allergic reactions. Mast cell activation syndrome is a narrower diagnosis. It describes people who have all three of these [2]:

• repeated attacks of symptoms that affect the whole body
• laboratory proof that mast cells released their messengers
• a response to treatment aimed at mast cells

Allergy specialists divide MCAS into three forms [3]:

Form	What it means
Primary (clonal)	Linked to an abnormal group of mast cells
Secondary	Linked to allergy or another underlying condition
Idiopathic	No cause has been found

What are the symptoms of MCAS?

Typical signs of mast cell activation affecting the whole body are [1][4]:

• sudden hives, flushing and itching
• headache
• stomach cramps and diarrhoea
• breathing symptoms and a blocked nose
• a fast heart rate
• low blood pressure with fainting or near-fainting

None of these on its own points to mast cells [4]. What matters is the pattern. “Systemic” means that at least two organ systems are involved at the same time, for example the skin and the gut, or the heart and blood vessels and the airways [4].

Many people who suspect MCAS mainly have long-term symptoms such as fatigue, brain fog, headache, nausea and poor sleep. According to the leading expert group, these symptoms do not on their own meet the criteria for mast cell activation. They are still real and deserve treatment [1].

How is MCAS diagnosed?

What are the consensus criteria?

The best-known criteria were published in 2012 by an international expert group, often called “consensus-1” [3]. All three must be met [4]:

What does the “20% + 2” tryptase formula mean?

Tryptase is one of the substances mast cells release, and it is the most specific marker of their activity [4]. The test compares two blood samples: one from a good day (your baseline) and one taken soon after an attack.

The level after an attack must be higher than your baseline plus 20% plus 2 ng/ml [4][5]. The unit ng/ml (nanograms per millilitre) tells how much tryptase there is in the blood.

Timing matters. The attack sample is best taken 1–4 hours after an attack starts and compared with a baseline sample taken when you are well [4].

A high baseline tryptase can point to other conditions. About 3 to 5 in 100 healthy people have extra copies of the gene for alpha-tryptase. This condition, hereditary alpha-tryptasemia, raises the baseline level [5].

Why are there two sets of criteria?

A second group of clinicians, led by Dr Lawrence Afrin, has proposed broader criteria called “consensus-2” [6]. The two groups disagree:

In practice, two people with the same symptoms may be told different things by different doctors. It helps to ask which criteria were used.

Can mould and mycotoxins activate mast cells?

Preliminary research Possibly. In 2018, researchers at Tufts University reviewed earlier studies on mycotoxins, the poisons that moulds make. They concluded that people exposed to mould and mycotoxins can have symptoms in many organs, including the lungs, the muscles and joints, and the nervous system. The effects of mycotoxins may come partly from inflammatory substances released by mast cells [8].

This was a narrative review: a summary of earlier research, not a new study. It does not show that mould exposure causes MCAS as defined by the consensus criteria.

This is also the link our histamine article describes. Mould exposure can add to the “histamine bucket” alongside diet, stress and slow breakdown by the DAO enzyme.

We could not find any study that measured how often people exposed to water-damaged buildings, or people with CIRS, meet the MCAS criteria (PubMed search, October 2026). The overlap is plausible, but it has not been measured.

How do MCAS, histamine intolerance and CIRS differ?

Three different problems can cause similar histamine-type symptoms. Picture the histamine bucket from our histamine article: too much histamine pours in, too little drains out, or the whole alarm system stays on.

• MCAS: too much release. Mast cells release too many messengers, in attacks. A rise in tryptase or other messengers confirms it [3][4].
• Histamine intolerance: too little breakdown. Usually the DAO enzyme in the gut does not clear histamine from food fast enough [9]. Our histamine article covers this in detail.
• CIRS: the alarm stays on. A chronic inflammatory illness. According to Dr Ritchie Shoemaker’s group, it follows biotoxin exposure in people who cannot clear the toxins effectively [10][11].

Expert opinion Shoemaker’s group has even commented on one sign often linked to mast cells: dermatographia, raised red lines that appear after you stroke the skin. In their 2018 consensus statement, they write that some clinicians see it as a sign of mast cell activation. In their view, it reflects high levels of the inflammatory marker C4a [10]. This is the group’s clinical opinion. It has not been tested against mast cell markers.

MCAS and CIRS side by side

	MCAS	CIRS
What happens	Mast cells release too many messengers (histamine, tryptase and others) in attacks [2]	Long-term inflammation of the innate immune system (the body’s fast first line of defence) after biotoxin exposure, in the Shoemaker model [10][11]
Typical symptoms	Attacks of flushing, hives, itching, stomach cramps, diarrhoea, wheezing, fast heart rate, low blood pressure [4]	Fatigue, aches, joint pain, brain fog, sinus and breathing symptoms, light sensitivity, thirst, temperature problems, numbness and tingling [10]
Trigger	Allergy, clonal mast cell disease or unknown [3]	Exposure, most often to water-damaged buildings [10][11]
Key tests	Tryptase after an attack against baseline (20% + 2); urine histamine breakdown products, 11β-prostaglandin F2α, leukotriene E4 [4][5]	Exposure history, symptom clusters, VCS test; MSH, MMP-9, C4a, TGF-β1, VIP, VEGF; HLA-DR typing [10]
Who diagnoses	Usually an allergist or immunologist	A doctor familiar with CIRS
Treatment approach	Medicines that block mast cell messengers or calm mast cells, prescribed by a doctor [4]	Ending the exposure, then the Shoemaker protocol [12]
Evidence base	International consensus criteria, but disagreement about broader criteria [6][7]	Mostly from one group of clinicians; independent trials lacking [12]

Can you have both MCAS and CIRS?

It is possible. The two are diagnosed with different tests, and nothing in either set of criteria rules out the other.

If mould toxins do activate mast cells [8], someone exposed to a water-damaged building could have both histamine-type attacks and the broader inflammatory picture of CIRS. How common this is has not been studied.

What should you do if you suspect MCAS, CIRS or both?

How strong is the evidence?

• Expert consensus MCAS has internationally published diagnostic criteria. But experts disagree about how broadly to apply them. Estimates of how common it is range from rare to up to 17% of the population [4][6][7].
• Preliminary research The link between mycotoxins and mast cells comes from a narrative review. No study has applied the MCAS criteria to mould-exposed people [8].
• Preliminary research The CIRS model and its tests come largely from Dr Shoemaker and colleagues. A 2024 review by CIRS practitioners found the Shoemaker protocol to be the only CIRS treatment with documented clinical efficacy. Independent controlled trials are lacking [12].

No study has looked at MCAS and CIRS together. So the honest answer is: a connection between mould, mast cells and CIRS is plausible but unproven. If your symptoms are tied to a building, it is reasonable to investigate both with your doctor, one test at a time.

Remember these

Test yourself: Can you explain why fatigue and brain fog alone do not meet the MCAS criteria? And how does MCAS differ from histamine intolerance?

What next?

• Read more about histamine and the histamine bucket.
• Read how CIRS is diagnosed.
• Find out whether your symptoms improve away from home.

References

1. Valent P, Akin C, Nedoszytko B, et al. Diagnosis, classification and management of mast cell activation syndromes (MCAS) in the era of personalized medicine. Int J Mol Sci. 2020;21(23):9030. PubMed
2. Akin C, Gülen T, Castells MC, Oude Elberink H, Valent P. Diagnosis and management of patients with mast cell activation syndromes: status 2026. J Allergy Clin Immunol Pract. 2026;14(1):19–28. PubMed
3. Valent P, Akin C, Arock M, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215–225. PubMed
4. Valent P, Akin C, Bonadonna P, et al. Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome. J Allergy Clin Immunol Pract. 2019;7(4):1125–1133.e1. PubMed
5. Valent P, Bonadonna P, Hartmann K, et al. Why the 20% + 2 tryptase formula is a diagnostic gold standard for severe systemic mast cell activation and mast cell activation syndrome. Int Arch Allergy Immunol. 2019;180(1):44–51. PubMed
6. Afrin LB, Ackerley MB, Bluestein LS, et al. Diagnosis of mast cell activation syndrome: a global “consensus-2”. Diagnosis (Berl). 2021;8(2):137–152. PubMed
7. Gülen T, Akin C, Bonadonna P, et al. Selecting the right criteria and proper classification to diagnose mast cell activation syndromes: a critical review. J Allergy Clin Immunol Pract. 2021;9(11):3918–3928. PubMed
8. Ratnaseelan AM, Tsilioni I, Theoharides TC. Effects of mycotoxins on neuropsychiatric symptoms and immune processes. Clin Ther. 2018;40(6):903–917. PubMed
9. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185–1196. PubMed
10. Shoemaker R, Johnson K, Jim L, et al. Diagnostic process for chronic inflammatory response syndrome (CIRS): a consensus statement report of the Consensus Committee of Surviving Mold. Internal Medicine Review. 2018;4(5):1–47. PDF
11. Shoemaker RC, House DE. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicol Teratol. 2006;28(5):573–588. PubMed
12. Dooley M, Vukelic A, Jim L. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment. Ann Med Surg (Lond). 2024;86(12):7248–7254. PubMed

Please note: this article is for information only and does not replace a diagnosis or treatment from a doctor. If you suspect MCAS, CIRS or any other illness, contact a healthcare professional.