Mast Cell Activation Syndrome (MCAS)

What is mast cell activation syndrome (MCAS)

In MCAS, mast cells release their chemicals at the wrong time, to the wrong trigger and in larger amounts than needed.  When this happens in a single system, like the upper respiratory tract, we call it hay fever; in the skin, hives/urticaria. When it occurs across multiple systems, it may represent MCAS. When this happens, it can cause symptoms that make people feel unwell or uncomfortable.

MCAS is not commonly recognised or diagnosed in Australia (there are complicated arguments around diagnosis and categorisation)[1,2]. Still, it is thought to co-exist or be implicated in people with conditions such as:

• Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)[3,4]
• Long COVID[5]
• Hypermobility and connective tissue disorders[6]
• Dysautonomia, especially POTS[6]
• Fibromyalgia[6]

Symptoms

MCAS can affect many parts of your body at the same time and affects each person very differently. Symptoms can fluctuate over time, and may include:

• Allergic-type reactions such as rashes, eczema, hives, or hay fever
• Sensitivity to chemicals or strong smells
• Headaches or migraine
• Fatigue
• Problems with thinking, memory, or mood
• Tinnitus (ringing in the ears)
• Shortness of breath
• Asthma
• Chest pain that is not related to heart disease
• Poor oral health despite good dental care
• Gut symptoms such as reflux, slow emptying time of the stomach (gastroparesis), diarrhoea, or constipation
• Urinary symptoms
• Easy bruising, fragile skin, or slow healing
• Frequent infections
• Joint or muscle pain
• Signs of inflammation without clear test results.

Why can mast cells affect so many parts of the body?

Mast cells are present in all vascularised tissues in the body, and are particularly concentrated in the tissues that touch the outside world[7], such as:

• Mouth
• Nose
• Airways
• Digestive system
• Skin
• Eyes
• Urogenital

Mast cells are also found around blood vessels, nerves, the brain, and the tissues around joints. Because mast cells are located throughout the body, problems with them can cause symptoms in many different systems at once.

What do mast cells normally do?

Mast cells release chemicals that help your body respond to infection, injury, or allergens. These chemicals can cause inflammation and signal other parts of the immune system to react. A normal reaction might be to an insect bite, or other injury to the skin – some inflammation is appropriate to ensure it doesn’t become infected.

In MCAS, cells may be triggered inappropriately by harmless things, like temperature changes, pressure on the skin, and hormonal changes, and may also result in a larger-than-normal response. One chemical released by mast cells is histamine, which is involved in allergic reactions.

Mast cells also have receptors for the same chemicals they release. This means that once they are activated, they may continue activating themselves and affect other parts of the body. A severe example of mast cell activation is anaphylaxis, a serious allergic reaction that can affect:

• Skin and Mucous Membranes: hives, itching, flushing, swelling of lips/tongue.
• Respiratory System: difficulty breathing, wheezing, throat tightness, coughing.
• Cardiovascular System: low blood pressure, rapid heartbeat, dizziness, fainting.
• Gastrointestinal System: nausea, vomiting, abdominal pain, diarrhea.
• Nervous System: anxiety, confusion, feeling very unwell.

Diagnosis

Diagnosing MCAS can be difficult. There is no single test that can reliably confirm MCAS, and the tests are not always reliable or readily available.

Doctors usually look for:

• Symptoms affecting two or more body systems
• Evidence of mast cell chemicals in blood or urine tests
• Improvement when using treatments that target mast cells or their mediators

Sometimes doctors may try mast-cell–targeted treatments and monitor for improvement in symptoms. This response can help support the diagnosis. Doctors will also check for other conditions that can cause similar symptoms.

Treatment

MCAS is currently considered a long-term condition with no cure, but many people can improve their quality of life by managing symptoms and live a normal, largely symptom-free life.

Symptoms may change over time, and things like illness, stress, trauma, or hormonal changes can make symptoms worse. Management usually involves three main steps.

Step 1: Identify and avoid triggers

Many people with MCAS find that certain things trigger symptoms.

Learning your triggers can help you manage flares. Some people find the idea of a “histamine bucket” helpful. This means your body can handle a certain amount of triggers, but when too many build up at once, symptoms flare.

The final trigger may seem harmless on its own, but it can cause symptoms when your “bucket” is already full. Keeping a symptom diary or using an app may help identify patterns and triggers.

Possible triggers include