Understanding MCAS

Mast Cell Activation Syndrome (MCAS) is part of a group of conditions called mast cell activation disorders, where immune cells called mast cells release their chemicals (mediators) too easily, too often or in excessive amounts. Mast cells are part of the innate immune system and play an important role in protecting the body, particularly in allergic reactions, but also in inflammation, tissue repair and defence against infections. They contain many different mediators, including histamine, tryptase and cytokines.

In MCAS, mast cells become overactive and release their contents out of proportion to a trigger or sometimes without a clear trigger, leading to episodic symptoms that can involve multiple body systems. While many people recognise mast cells for causing immediate allergic symptoms such as itching, hives, swelling or breathing difficulties, the wide range of chemicals they release and their presence throughout the body means that symptoms can vary widely in both type and severity.

MCAS sits under the broader category of mast cell activation disorders (MCAD), which includes any condition where mast cells are activated.

These disorders are grouped based on the cause:

• Primary: due to abnormal mast cells (increased numbers or function) e.g. systemic mastocytosis

• Secondary: normal mast cells that are “hyperresponsive” to triggers (e.g. both IgE and non IgE allergic reactions)

• Idiopathic: no identifiable cause

MCAS is included under the idiopathic group, where no clear underlying cause is found.

Typical signs and symptoms of MCAS tend to be episodic and affect at least 2 organ systems. This may include:

• Skin: flushing, itching, hives, swelling

• Heart: palpitations, low blood pressure

• Lungs: wheezing, difficulty breathing

• Gut: diarrhoea, abdominal pain, severe bloating

MCAS is diagnosed based on a combination of symptoms, test findings and response to treatment—there is no single test that confirms it. Instead, it is defined when all the following are present:

• A history of recurrent, severe and systemic (whole-body) episodes of mast cell activation. These episodes often involve multiple body systems at the same time and occur repeatedly over time.

• Evidence that mast cells are releasing their mediators, which may sometimes be detected through testing (for example, markers like tryptase can rise during an episode).

• Clear improvement with medications that target mast cell mediators or block their effects (such as antihistamines).

This is a short checklist created by the Gaudiani Clinic to help you identify whether mast cell activation may be contributing to your symptoms.

• R – Reactions
  Do you react to foods, medications, scents, or body products (e.g. skincare, cleaning products)?

• A – Alcohol sensitivity
  Do you feel flushed, itchy, or unwell after alcohol or alcohol-based products (e.g. hand sanitiser)?

• S – Skin symptoms
  Do you frequently experience rashes, hives, or itchy skin?

• H – Heat sensitivity
  Do you feel unwell, fatigued, itchy, or swollen after heat or sun exposure?

• P – Pain
  Do you regularly experience pain (such as headaches, joint, muscle, or digestive pain)?

• F – Fatigue
  Do you often feel unusually tired or fatigued without a clear reason?

What does this mean?
If you answered “yes” to 3 or more of these, mast cell activation may be contributing to your symptoms. This is not a validated diagnostic tool, but it can help identify whether it may be worth exploring a diagnosis of MCAS.

Given MCAS is a diagnosis of exclusion, your doctor should review your medical history to make sure there is not a better explanation for your symptoms. If you have specific allergy triggers, it may be appropriate to have skin prick testing or RAST testing (blood test for specific allergens like dust mite). In addition, a baseline tryptase level should be measured and compared to a level taken between 30mins to 2hrs after an episode. A diagnosis of MCAS is supported by an elevation in tryptase of >20% +2 compared to baseline.

Other testing available in Australia includes urine n-methylhistamine and chromogranin A. However, these are not currently recommended as part of the routine investigation of MCAS. Depending on where you live, there may be additional testing available including urinary and blood histamine levels, blood prostaglandin D2 and 11-B- prostaglandin F2a and urinary leukotriene E4. Currently these are not available or validated for the diagnosis of MCAS within Australia.

This is an area of ongoing debate in the medical community. According to current Australasian Society of Clinical Immunology and Allergy (ASCIA) guidelines, a measurable rise in tryptase during a reaction is required to diagnose MCAS. These recommendations are based on earlier criteria (often called “consensus-1”), which place strong emphasis on tryptase as the key laboratory marker of mast cell activation.

However, some experts have raised concerns about this strict approach, as many people with symptoms suggestive of MCAS may not show a rise in tryptase. A newer approach (“consensus-2”) suggests that increases in a broader range of mast cell chemicals—such as histamine or prostaglandins—can also support the diagnosis, particularly when someone has ongoing, unexplained symptoms affecting multiple body systems.

In simple terms, while current local Australian guidelines rely heavily on tryptase, other experts believe MCAS may still be present even if tryptase is normal, depending on the overall clinical picture.

Start with seeing your local GP to exclude other potential causes for your symptoms and whether you need a referral to an immunologist for specific allergy testing.

Simple things to trial can include over the counter histamine receptor 1 blockers and prescription histamine receptor 2 blockers such as famotidine, to see if there is a significant improvement in your symptoms.

If antihistamines haven’t been enough to control your symptoms, the next step may be to trial medications that help stabilise mast cells.

This can include medications such as ketotifen and sodium cromoglycate. Ketotifen works as both an antihistamine and a mast cell stabiliser. It is available over the counter as an eye drop and can also be made into a capsule or liquid through a compounding pharmacy with a prescription. Sodium cromoglycate may be particularly helpful if gut symptoms are prominent. In Australia, it is also available over the counter as an eye drop or it can be compounded into a liquid or capsule with a prescription.

It can also be helpful to look beyond histamine, as mast cells release many different chemicals. For example, montelukast is a medication commonly used for asthma and allergies that targets leukotrienes and may help if you experience symptoms such as wheezing or shortness of breath. This is available through regular pharmacies with a prescription.

Low dose naltrexone may also be considered. It can help reduce inflammation and support the way mast cells behave in the body. This medication needs to be compounded and is usually taken as a liquid or capsule.

Omalizumab (Xolair) is a specialised injectable medication that reduces allergic-type mast cell activation. In Australia, it is available under the PBS for conditions such as severe allergic asthma and chronic spontaneous urticaria, usually through an immunologist. If you have MCAS alongside these conditions, you may be eligible.

In addition to medications, it is important to look at factors that may be contributing to ongoing symptoms. This can include:

• Identifying and reducing exposure to triggers in your environment (such as dust mites, chemicals or specific foods)

• Trialling a low histamine diet as a short-term strategy for symptom relief while working out your individual triggers

• Assessing how well your body breaks down histamine. This involves two main pathways (DAO and HNMT), which can be affected by genetics, nutrient levels (such as vitamin C and vitamin B6) and gut health

• Addressing constipation and faecal loading, as this can worsen symptoms

• Trialling natural mast cell stabilisers such as luteolin

Finally, it is important to consider and treat any associated conditions, such as POTS or hypermobile conditions. Many people benefit from a team-based approach, working with different health professionals to support their overall health.

If you’re looking to learn more or find support, these organisations provide reliable information and practical resources: ‍

• Mast Cell Matters Podcast. A podcast covering MCAS and related conditions, with insights from clinicians and patient experiences.

• The Australasian Mastocytosis Society (TAMS). An Australian-based organisation providing education and support for people with mast cell disorders.

• Mast Cell Action. A UK-based charity offering clear, patient-friendly information on MCAS, along with resources, research updates, and advocacy.

• ASCIA Position Paper. A detailed guideline from Australia’s peak allergy and immunology body designed for healthcare professionals. It outlines how MCAS is investigated and diagnosed and may be helpful if you would like a deeper understanding of the testing and diagnostic process.