MCAS testing

Testing guidelines in Australia and Aotearoa New Zealand for mast cell activation syndrome (MCAS) are informed by international consensus criteria, including key updates in 2019, 2021 and 2026, which outline the requirements for demonstrating mast cell activation (MCA) using validated markers.^1,4,11

Testing by exclusion

Because MCAS requires the exclusion of other possible causes, patients undergoing assessment will generally require additional investigations for conditions that may cause similar symptoms, including gastrointestinal symptoms, facial flushing or rashes. The testing required will depend on the individual’s presentation, medical and family history and other clinical findings, including consideration of conditions such as coeliac disease or rosacea. Common investigations may also include evidence-based allergy testing, such as skin prick testing, to identify or rule out allergies to foods, environmental allergens, medications or insects that may explain symptoms or contribute to secondary MCA.²

To establish what testing is needed to rule out other common conditions, please discuss your full symptom history with your general practitioner (GP).

There are only a limited number of validated tests utilised in the diagnosis of MCAS.^2,12 However, symptoms often overlap with those of other chronic or immune-based conditions, which may mean patients undergo a broader range of tests than those listed below. Questions about the purpose or relevance of any additional testing should be directed to the ordering specialist.

Tests for MCAS

Blood tryptase testing remains the ‘gold standard’ mediator test for MCAS evaluation and is central to validated diagnostic criteria.¹ While a 2026 publication on MCAS management by authors of the international MCAS consensus criteria recognised the potential value of additional mast cell mediators, including urinary N-methylhistamine and urinary metabolites of prostaglandin D₂ (PGD₂) and leukotriene C₄, several of these additional mediator tests are not currently available, with some tests for these mediators having been withdrawn from our market on numerous occasions given lack of reliability.¹

Although histamine testing also has accuracy limitations, including false-positive or -negative results due to improper handling, it is still available in Australia and Aotearoa New Zealand through blood tests (serum or plasma histamine) and spot or 24-hour urine tests (urinary N-methylhistamine). Blood testing usually does not require dietary preparation, while urine testing generally requires a strict low-histamine diet before and during collection, as per laboratory instructions.

When histamine testing is ordered by a GP or specialist, results should be interpreted by the investigating or managing immunologist, together with other clinical and pathological findings, to establish their relevance to the individual’s broader investigations, symptom management, and MCAS assessment. Elevated histamine levels in blood or urine, whether isolated or repeated, do not confirm an MCAS diagnosis on their own or eliminate the need to investigate other possible causes, such as histamine intolerance.^1,2

Genetic testing 

Genetic testing is not routinely required for all patients undergoing assessment for MCAS. However, where a clonal MCAD is suspected, testing may include investigation for activating KIT mutations, particularly KIT D816V, which can sometimes be detected in peripheral blood. Initial investigation for suspected clonality may therefore include blood testing at the discretion of a GP or specialist.^1,2,4,10

Further assessment may include mast cell staining in tissue samples, including gastrointestinal biopsies where clinically indicated. CD117 helps identify mast cells, while aberrant CD25 and/or CD2 expression may support clonality.^1,10 However, endoscopy or colonoscopy with mast cell staining is not a routine diagnostic investigation for MCAS and should be guided by the investigating specialist and individual patient presentation. Mast cell staining or increased mast cell numbers alone do not establish MCAS, and, likewise, a negative peripheral blood test for clonality does not always rule out the need for further tissue investigation.^1,2 Results from blood or tissue testing should always be interpreted by the investigating/managing immunologist alongside other clinical and pathological findings before a diagnosis is established.

Hereditary alpha tryptasemia (HαT) testing

HαT testing may also be considered where clinically indicated. In Australia, locally available HαT testing currently requires a persistently elevated baseline serum tryptase to meet laboratory eligibility criteria. International testing may also be available where a clinician suspects HαT, but the patient does not meet local testing criteria. HαT results from additional alpha-tryptase-encoding copies of the TPSAB1 gene and can influence interpretation of basal tryptase levels.^1,2,14 HαT is not itself an MCAS diagnosis or subtype, and many people with the trait are asymptomatic.^1,2,14

Unvalidated testing

It is critical that patients are aware of the difference between recognised, evidence-based tests and unproven or non-evidence-based options, including wellness or direct-to-consumer tests offered by alternative or allied health practitioners, or available online.¹²

Unproven tests may include hair analysis, organic acids testing, food sensitivity panels, bioresonance, electrodermal testing, and other panels marketed for broad symptoms or proposed underlying “toxin burden” and “imbalances”.²

Such tests can entail high out-of-pocket costs, generally have no role in primary/traditional healthcare, and, importantly, are not part of recognised MCAS investigations or evidence-based allergy and clinical immunology testing. If you are offered testing by doctors or allied health providers and it is presented as a way to confirm MCAS rather than to investigate other conditions or support allied health practices outside primary medical diagnosis and treatment, we recommend clarifying its intended purpose with the provider or service.

If you are unsure about the evidence supporting a test for an MCAS investigation or another immunological assessment, such as allergy diagnosis, we encourage you to discuss it with your current or intended immunologist before making treatment changes.

If you have already undergone testing you suspect may be unproven and were advised to make lifestyle, medication or other treatment changes based on the results, discuss the test and any findings with your immunologist so they can help determine whether further evidence-based investigation is appropriate and advise on next steps.

MCAS testing summary

An MCAS assessment requires that other possible causes of the symptoms be ruled out. Testing to investigate or continue excluding other, more likely explanations may therefore continue even after an MCAS diagnosis has been made. The following tests may also form part of a validated MCAS assessment. Please refer to your investigating or treating immunologist for guidance on which tests are appropriate in your individual case.

• Baseline serum tryptase – Measures baseline tryptase levels. In MCAS, baseline tryptase may be normal.^1,13
• Event tryptase – Ideally collected within 1–4 hours of a significant episode and compared against baseline.
• Additional mediator testing – Where available, may include urinary N-methylhistamine and urinary metabolites of PGD₂ and leukotrienes, including LTE₄.¹ In Australia and Aotearoa New Zealand, urinary N-methylhistamine testing is available, while PGD₂ and leukotriene metabolite testing is not currently available through locally accredited clinical laboratories.²
• Clonal testing – When a clonal MCAD is suspected, testing may include KIT D816V and mast cell markers such as CD25, CD2, or CD30 in blood or tissue. Blood testing for KIT D816V is customary in the first instance and may inform specialist consideration on the need for further tissue testing.^4,10,38
• HαT testing – May be considered where clinically indicated. Reminder: HαT is neither a diagnostic criterion nor a subtype of MCAS.^1,2,14

*Neither baseline nor event tryptase alone establishes MCAS.^1,13

Please note: Because mast cell mediators can be difficult to detect during a significant rise, some testing may need to be repeated on more than one occasion. However, the need for repeat testing will depend on your individual circumstances and should be guided by your GP or, ideally, your investigating/managing immunologist. Repeated testing without a clear medical purpose is unlikely to be helpful and may result in high cost or stress. Where relevant, your immunologist can also advise your GP which tests, if any, should be monitored routinely.

Need more information?

While TAMS cannot advise what testing is needed in your individual case or comment on the testing practices of individual GPs, specialists or allied health providers, we can provide general information about MCAS testing and commonly used investigations.

If you need general guidance, including information about where a test you have been asked to undertake may be available in Australia or Aotearoa New Zealand, you are welcome to contact us .