Diagnosing MCAS
Diagnosing MCAS requires a systematic, stepwise approach, which means that it can take a considerable amount of time for individuals to receive a formal diagnosis of MCAS.
Key steps in diagnosis MCAS include recognising clinical symptoms, investigating response to treatment, undertaking mediator tests and ruling out other diagnoses.
Sometimes, not all of these steps are, or can be, taken. In these cases, people are typically diagnosed with ‘suspected MCAS’.
This stepwise process is reflected in the published diagnostic criteria for the condition (Molderings et al., 2011; Valent et al., 2019) and in the diagnostic algorithm proposed by Giannetti et al., 2021).
If a person fulfils each of these four sets of criteria, a confident MCAS diagnosis can be provided.
Frequently this process requires a ‘trial and error’ approach, and people often wait a long time for a definitive diagnosis.
The uncertainty of this situation can be very difficult for people who suspect that they have MCAS but have not had their condition diagnosed.
If you would like to access more information related to MCAS diagnosis, please see the Diagnostic Support section of our Resources for Medical Professionals page, as well as the MCAS Bibliography.
Useful papers
The current consensus diagnostic criteria for mast cell activation syndrome(s) (MCAS[s]) were first established in 2012 and updated in 2019. This diagnosis has been attached to multiple medical conditions not intended as part of the diagnosis. In this article, the diagnostic criteria are reviewed and other diseases in the differential diagnosis outlined.
These papers are key resources for diagnostic tests, outlining The Utility of Measuring Urinary Metabolites of Mast Cell Mediators in Systemic Mastocytosis and Mast Cell Activation Syndrome.
Expand the sections below to learn more about these steps in MCAS diagnosis.
Clinical symptoms
The first step is recognising the presence of typical clinical symptoms across multiple body systems.
MCAS symptoms are often episodic or wax and wane and their severity can fluctuate over time.
Symptoms can include:
- dermatologic symptoms: such as flushing/redness, hives or wheals, itching with or without a rash, swelling
- gastrointestinal symptoms: such as bloating, stomach pain/cramps, reflux, nausea, feeling or being sick, diarrhoea, constipation, dumping syndrome
- respiratory symptoms: such as sore throat, hoarseness, wheezing, shortness of breath, throat swelling, stridor
- cardiovascular symptoms: such as chest pain, low blood pressure, fast heart rate, fainting or light headedness
- naso-ocular symptoms: such as nose congestion, eye watering and itching
- neurological problems: such as headache, brain fog (memory or concentration difficulties), numbness, pain or tingling skin, anxiety, behavioural issues, rages
- musculoskeletal issues: such as joint and muscle pain, osteoporosis (brittle bones), loss of bone mass
- genital and urinary issues: such as genital pain or swelling, pain when urinating, vaginal pain, discharge or itching, bladder urgency or loss of control
- extreme tiredness
- food allergies or intolerances
- anaphylaxis
Response to treatment
Another step in the diagnosis of MCAS is often referred to as a ‘test of treatment’. It is underpinned by the theory that, if a person responds to MCAS treatment, this is evidence to suggest that the individual has MCAS.
Not everyone with MCAS will respond to the same medicines, so finding one that works can be a process of trial and error.
Common medications that can be used for MCAS include:
- H1 antihistamines e.g. loratadine, cetirizine, and fexofenadine
- H2 antihistamines e.g. cimetidine, famotidine, nizaditine
- Mast cell stabilisers e.g. ketotifen, sodium cromoglicate
- Anti-leukotrienes e.g. montelukast
- Anti-prostaglandins e.g. aspirin, ibuprofen and naproxen
- Vit C, Vit D, quercetin, luteolin
Mediator tests
Ideally, the previous steps are combined with a biochemical assessment to show evidence of elevated mediator release from mast cells.
- This can be challenging because mast cell mediators may only be elevated during an MCAS episode and then return to normal levels. Therefore, the test needs to be done when the symptoms of MCAS are present.
- These tests also need to be conducted by an experienced healthcare provider, using an accredited laboratory to ensure that the test samples are handled appropriately.
- The specific mediators of interest, and the thresholds required to attribute MCAS, are the subject of ongoing research and debate among the medical community.
No single mediator test is definitive; a positive result is not to say that a person certainly has MCAS and, similarly, a negative result is not sufficient to rule out an MCAS diagnosis. However, when considered alongside other diagnostic evidence, these mediator tests can provide reasonable confidence in a diagnosis.
Tryptase is often one of the first mediators which is tested for in people with a suspected mast cell disorder (using a blood test), and it remains the only mediator test with a specified increase in levels for diagnosis. However, a tryptase test must be conducted within a short time period (less than 4 hours) after an MCAS ‘flare’ and compared to baseline levels collected 24–48 hours later. Other mediator tests carried out in the UK include tests for urinary N-methylhistamine and prostaglandins D2, DM and F2α. Mediator tests are becoming increasingly available on the NHS.
Rule out other diagnoses
Finally, it is important to discount other potential diagnoses and/or determine whether an individual has multiple conditions (with or without MCAS).
Common comorbidities include connective tissue disorders such as Ehlers Danlos Syndrome (EDS), and Marfans, Postural Orthostatic Tachycardia Syndrome (PoTS), Type 2 Diabetes, Anaphylaxis, Autoimmune diseases, Autoinflammatory conditions, Vasculitis and Addison’s Disease.
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