Mast cell activation syndrome (MCAS)

In the past, the strict medical guidelines required a patient to have repeated episodes of anaphylaxis, meaning acute and life-threatening allergic shock, to be given a diagnosis of MCAS. This meant that many people who suffered from chronically overactive mast cells, but without the acute episodes, were left without a diagnosis and without help. Lessons from modern research have therefore been brought together in the Consensus-2 guideline, which broadens the definition of MCAS.

Today we know that it is not only people with inherited genetic changes who can have disturbed mast cell function. Mast cell activation can also be caused by other diseases, and can for example begin after an infection.

The term now also covers a constant release of substances from the mast cells, called "chronic mediator release syndrome". This means you can have ongoing inflammation in the body, where the mast cells constantly leak inflammatory substances, without having acute allergic shock.

What mast cells normally do

Mast cells are part of your body's defence system. They sit in the tissues that meet the outside world (your skin, gut, and airways) and act like tiny alarm stations. When they sense a threat, such as an insect sting, they release a mix of substances that cause redness, swelling, itching, and other reactions that help the body respond. More than a hundred different substances can be released. Several of them affect how inflammation is controlled, and how blood vessels work. Because mast cells are found all over the body, these substances can affect several parts of the body at the same time.

What happens in MCAS

An MCAS episode can sometimes look like an allergic reaction, even when you have no clear allergy. But unlike a classic allergy, where the mast cells mainly empty out histamine in an explosive reaction, MCAS is marked by substances leaking out of the mast cells, or being released in too large amounts. In other words, the mast cells do not work as they should.

MCAS often comes in episodes: symptoms flare and then ease, and they often involve two or more parts of the body at once. Symptoms vary a lot between people, but common ones include:

• Skin: flushing (sudden redness, often of the face and chest), hives, itching, swelling
• Stomach and gut: cramping, abdominal pain, nausea, vomiting, diarrhoea
• Heart and circulation: lightheadedness, palpitations, drops in blood pressure, faintness, bruising
• Airways: wheezing, shortness of breath, throat tightness, nasal congestion

Many people also describe tiredness, headache, and brain fog.

Episodes are often set off by something. Examples include:

• Heat or hot water
• Cold, or sudden temperature changes
• Alcohol
• Certain medicines and, sometimes, contrast dye used in scans
• Physical stimuli such as pressure, friction, or exercise
• Emotional stress
• Hormonal changes
• Infections
• Certain foods
• Insect stings

Keeping track of what comes before an episode can help you and your doctor spot your personal triggers.

Anyone can get MCAS, but it is diagnosed more often in women (roughly 3:1). The changed function of the mast cells can sometimes be due to an inherited difference. But it can also be due to an underlying condition. MCAS seems to be fairly common in, for example, POTS, long covid, or hypermobility. In those conditions the mast cells are probably switched on by the inflammatory environment or by connective tissue factors in the body.

The exact biological link between the different conditions that can be seen with MCAS is still being studied.

For a diagnosis, doctors look for the following:

Typical symptoms: Recurrent episodes of mast cell activation affecting at least two organ systems, for example skin and gut, or gut and low blood pressure.
Response to treatment: Symptoms improve with medicines that block mast cell substances or calm the mast cells.
A plausible cause: There is an underlying reason why the problems began (for example an infection).

Doctors also need to explore whether there could be other causes of the symptoms. Many conditions can look similar, including allergies, thyroid problems, and diseases of the stomach and gut.

Measuring raised levels of the inflammatory or blood-vessel-affecting substances is desirable, but usually hard to do in ordinary healthcare. Many of the substances can only be identified with methods used in research studies.

There is no cure for MCAS, and no medicine is approved specifically for it. But most people improve a lot with a stepwise plan. Treatment aims to avoid triggers, to calm the mast cells, and to block the substances they release. It is usually built up in steps.

Avoiding triggers. Identifying and avoiding your personal triggers is the foundation of treatment.

Everyday medicines (first steps)

• H1 antihistamines (for example desloratadine, loratadine, cetirizine, or hydroxyzine). These are the mainstay and can often be increased above the standard dose under medical follow-up.
• H2 antihistamines (for example famotidine), especially helpful for stomach symptoms and as an add-on for skin and circulation symptoms.

Added medicines if needed

• Mast cell stabilisers
• Leukotriene blockers

Which combination suits you depends on your symptoms, your triggers, and any other conditions, so the plan should be built together with a doctor.

Small, consistent steps help many people:

• Keep a symptom-and-trigger diary. It helps you spot patterns and shows your doctor how you are doing.
• Take medicines regularly, not only during flares, if your doctor advises preventive dosing.
• Address overlapping conditions. If you also have POTS, allergies, or gut problems, treating those together usually works better than treating each alone.

MCAS varies from person to person. Many people feel better once triggers have been identified and treatment is in place.

Call 112 (or your local emergency number) if you have signs of a severe allergic reaction (anaphylaxis):

• Difficulty breathing, wheezing, or throat tightness
• Swelling of the lips, tongue, or throat
• A sudden drop in blood pressure, collapse, or fainting
• Widespread hives with feeling very unwell
• A severe reaction after a sting, food, or medicine

Contact your health centre or call 1177 (or your local healthcare provider) if:

• Your episodes are new, more frequent, or clearly getting worse
• Your current medicines are no longer controlling symptoms
• You have had a reaction and are not sure what triggered it