An Overview of Mast Cell Activation Syndrome (MCAS)

What is Mast Cell Activation Syndrome?

Mast Cell Activation Syndrome (MCAS) is a condition which can develop in children or adults. MCAS forms part of a spectrum of mast cell disorders. People with MCAS may also have other mast cell disorders such as mastocytosis or hereditary alpha tryptasemia syndrome (HATS).

In people affected by MCAS, chemicals called mast cell mediators are released too frequently or abundantly, and/or in response to triggers that are not typically considered to be harmful, for example; foods or chemicals in the environment. This can lead to a wide range of symptoms that affect multiple parts of the body (Figure 1).

Triggers and symptoms of MCAS vary greatly between individuals. Triggers can include fragrances, exercise, stress and changes in temperature (Figure 2).

MCAS symptoms can come and go and may often change over time within the same person. This can make it difficult to identify specific triggers, and the number of triggers and severity of symptoms may continue to increase as the condition progresses.

More research is needed to understand MCAS. Sometimes the condition occurs in family groups, suggesting that there may be genetic causes of MCAS.

What is a mast cell?

Mast Cells are a type of blood cell found in all parts of the body. They are a key part of the immune system. Mast cells detect different types of triggers and tell other immune cells how to respond.

Mast cells are known as 'police officers’ of the immune system' – spotting signs of trouble and calling for back-up when needed.

In a healthy state, mast cell mediators create a number of protective responses in the body to help fight infection and promote healing. In someone with MCAS, where these mediators are released too frequently, they can affect the body in multiple ways - causing multiple symptoms in different parts of the body at the same time.

How is MCAS diagnosed?

We know how important getting a confirmed diagnosis of MCAS can be. Published guidance recommends four diagnostic stages that should be completed so that your doctor feels comfortable confirming a full diagnosis of MCAS. Getting this diagnosis can be a complex and lengthy process taking many years, particularly due to the challenges involved with testing for mast cell mediators.

Stage 1

MCAS is considered a multi-systemic condition. Because of the complex pattern of symptoms, no two people are likely to experience MCAS in exactly the same way. Symptoms can also vary over time, often waxing and waning.

It is common for someone with MCAS to have mild and controllable symptoms for a long time, but a stressful event like an infection, an operation or an illness – for example COVID-19 – can cause a dramatic increase in symptom severity or frequency.

Stage 2

This stage ascertains if MCAS symptoms are improving with certain medications. This may be referred to as a medication trial - if a person’s symptoms get better after taking a known MCAS medication, then a diagnosis is more likely.

You can find out more about MCAS medications at https://www.mastcellaction.org/management.

Stage 3

There are tests that can be used to identify whether higher than normal levels of chemical mediators are present in the body. These mediators can be tested for in the blood or in the urine.

Due to the allergic-type symptoms of MCAS, testing for IgE-mediated allergies is often one of the first tests to be performed by doctors, usually as a skin prick test or by taking a blood sample for RAST testing. In idiopathic MCAS these are usually found to be inconclusive or negative.

Other mast-cell mediators can be tested for with a 24-hour urine collection. These include methylhistamine and prostaglandins. Elevated results of these can be suggestive of MCAS but having normal levels doesn’t rule out MCAS and repeated testing may be needed.

It is often better to take these tests during a flare, when symptoms may be particularly severe. In addition, some tests may need to be performed in the absence of particular medications, which will need to be carefully discussed with a health professional.

Biopsies can also be taken from the gut, bladder or skin, where the presence of high or abnormal mast cell numbers can be supportive of a diagnosis of MCAS or mastocytosis.

Unfortunately, there are currently no genetic tests identified for diagnosing MCAS – but research is underway to change this.

Stage 4

Eliminating any other possible causes of symptoms is an important stage of the diagnostic process as there are many conditions that overlap with MCAS such as chronic fatigue syndrome, Lyme, and asthma, for example.

Due to the wide-ranging symptoms associated with MCAS there can be an overlap with the symptoms experienced with a number of other conditions. During any diagnostic process, it is important to ensure that other potential diagnoses are not missed. In addition, more than one condition can exist at the same time. This may mean additional investigations such as endoscopy, colonoscopy, imaging and biopsies are required.

Anaphylaxis

People who have MCAS are at an increased risk of having an Anaphylactic reaction after encountering a trigger. Anaphylaxis is a potentially life-threatening allergic reaction, it has a rapid onset of symptoms and it is important to be aware of the ABC signs:

Airways: look for a persistent cough, swollen tongue or lips, and difficulty swallowing.

Breathing: look for difficulty breathing and wheezing.

Circulation/Consciousness: look for reduced blood pressure, confusion, and collapsing.

Pre-loaded adrenaline auto-injectors, commonly known as EpiPens, are prescribed to combat anaphylaxis. If you are at risk of anaphylaxis you need to carry your auto-injector at all times, and give an injection as soon as any symptoms of anaphylaxis occur. Always call an ambulance immediately following injection, even if there is a drastic improvement.

Comorbidities

People who have MCAS often have at least one additional condition.

Common comorbidities include connective tissue disorders such as Ehlers Danlos Syndrome (EDS) and Marfans, dysautonomia, such as postural orthostatic tachycardia syndrome (POTS), and type 2 diabetes.

The relationship between MCAS and many of these comorbidities is yet to be fully understood, and more research is required.

Managing MCAS

At present, sadly, there is no cure for MCAS. The aim of treatment is to reduce the severity of symptoms and improve quality of life. There are two main methods for symptom management, the first is through a self-management approach and the second is through the use of medicinal products. Ideally, these two approaches will be combined to achieve the best level of control over the symptoms of MCAS.

Self-management

Avoiding triggers is a key part of managing MCAS and relieving symptoms. If you have been able to identify specific triggers of your symptoms – for example, specific foods or chemicals, exercise or stress – these triggers should be avoided as much as possible to prevent a reaction.

This can include adopting specific diets such as low histamine or FODMAPS; controlling blood sugar fluctuations can also be beneficial. Some people may need to explore a combination of diets depending on their specific triggers, and if this is complicated, seeking help from either a dietician or nutritionist with knowledge of MCAS can be helpful.

This can also mean careful management of your personal environment, ensuring your home is free of your known triggers or those commonly understood to affect people with MCAS. Scented products such as candles, perfumes and air fresheners are classic examples of common triggers. Cleaning products can also be problematic for some.

Of course, in many cases, MCAS triggers are challenging to identify and new triggers may continue to develop over time. Sometimes, it is not always practical or even possible to avoid every trigger all of the time, particularly in public spaces.

Certain medicines, such as codeine, are also known to trigger MCAS symptoms. Some people with MCAS also benefit from avoiding non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen. Understanding your unique set of triggers can help to better identify which medicines and excipients should be avoided. This should be done with the support of a medical professional.

Many people find they experience significant relief upon isolating their triggers and avoiding them where possible.

Medical management

Multiple medicines can be used to help alleviate the symptoms of MCAS. These include mast cell stabilisers; which help restore stability to the mast cell and reduce its reactivity to different triggers, and mediator blockers; which block the release or the effect of different mediators released by the mast cell.

Due to the variation in triggers, mediator release and symptoms across individuals with MCAS, a medical treatment that works for one person may not work for another and the response to treatment is not always predictable.

An added complication for the treatment of MCAS arises from the possibility that some drugs (or the additives or preservatives in them) can be triggers for MCAS and this may cause an adverse reaction to a medicine. This can make it a lengthier and more complicated process to identify a successful medical treatment regimen for someone with MCAS. However, with a dedicated ‘trial and error’ approach, under careful medical guidance, many people with MCAS are eventually able to find a medical management process that works for them.

You can find more detail about mast cell activation syndrome here: https://www.mastcellaction.org

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