Diagnosing MCAS

Diagnosing MCAS requires a systematic, stepwise approach, which means that it can take a considerable amount of time to receive a formal diagnosis of MCAS.

If some, but not all, of these steps have been undertaken people are frequently considered to have a diagnosis of suspected MCAS:

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 (meaning that they go and come back) and their severity can fluctuate over time.

Symptoms can include:

  • dermatologic (skin) symptoms: such as flushing/redness, hives or wheals, itching with or without a rash, swelling
  • gastrointestinal (digestive system) symptoms: such as bloating, stomach pain/cramps, reflux, nausea, feeling or being sick, diarrhoea, constipation, dumping syndrome
  • respiratory (lungs & breathing) symptoms: such as sore throat, hoarseness, wheezing, shortness of breath, throat swelling, stridor
  • cardiovascular (heart & blood vessels) symptoms: such as chest pain, low blood pressure, fast heart rate, fainting or light headedness
  • naso-ocular (nose & eyes) symptoms: such as nose congestion, eye watering and itching 
  • neurological problems (brain & nerves): such as headache, brain fog (memory or concentration difficulties), numbness, pain or tingling skin, anxiety, behavioural issues, rages
  • musculoskeletal (bones & muscles) 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.

 

Please seek medical support:

Some of the medicines mentioned in this list are available over the counter from the pharmacist, but many require a prescription from your doctor. We would recommend that you seek medical guidance either from a pharmacist or other medical health professional when using any of these medicines to manage the symptoms of MCAS.

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, or determine whether an individual is suffering multiple conditions (with or without MCAS).

Conditions which should be considered, include other causes of anaphylaxis, autoimmune diseases, autoinflammatory conditions, vasculitis or Addison’s.

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 may have to 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 have been affected by this, please do reach out for further information and support from the charity.

If you are a medical professional and would like to access more information related to MCAS diagnosis, please see the Diagnostic Support section of the Resources for Medical Professionals page, and the MCAS Bibliography.

Further reading:

Weiler CR. Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis. J Allergy Clin Immunol Pract. 2020;8(2):498-506.

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